Trapping and manipulation of nanoparticles with light and electric field

ABSTRACT

A nanotweezer and method of trapping and dynamic manipulation thereby are provided. The nanotweezer comprises a first metastructure including a first substrate, a first electrode, and a plurality of plasmonic nanostructures arranged in an array, and a trapping region laterally displaced from the array; a second metastructure including a second substrate and a second electrode; a microfluidic channel between the first metastructure and the second metastructure; a voltage source configured to selectively apply an electric field between the first electrode and the second electrode; and a light source configured to selectively apply an excitation light to the microfluidic channel at a first location corresponding to the array, thereby to trap a nanoparticle at a second location corresponding to the trapping region.

RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional PatentApplication No. 63/056,922, entitled “TRAPPING AND MANIPULATION OFNANOPARTICLES WITH LIGHT AND ELECTRIC FIELD,” filed Jul. 27, 2020, theentire contents of which are incorporated herein by reference.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH & DEVELOPMENT

This invention was made with government support under Award Number1933109 award by the National Science Foundation. The government hascertain rights in the invention.

BACKGROUND 1. Field of the Disclosure

This application relates generally to the optical manipulation ofnanoscale objects. More specifically, this application relates to anoptically controlled nanotweezer, and to the trapping and dynamicmanipulation of nano-objects thereby.

2. Description of Related Art

Optical tweezers have been studied as a tool for the non-invasivetrapping and manipulation of colloidal particles and biological cells.However, the diffraction limit presents difficulties for the low-powertrapping of nanometer-scale objects. In some comparative approaches,significantly increasing the laser power may provide enough trappingpotential well depth to trap nanoscale objects. For example, somecomparative approaches implement electrothermoplasmonic (ETP) trapping,in which an ETP flow is induced to initiate rapid particle transporttowards a plasmonic hotspot for trapping at the hotspot. However,because such approaches result in trapping at or near the laser focus,the optical intensity required for trapping causes photo-toxicity andthermal stress where the nanoscale objects are biological specimens.

Accordingly, there exists a need for a nanotweezer capable of trappingand dynamically manipulating nanometer-scale objects, includingbiological specimens, at locations that are on the order of microns awayfrom the high-intensity laser focus.

SUMMARY

Various aspects of the present disclosure relate to devices, systems,and methods for the trapping and dynamic manipulation of individualnano-objects by an optically-controlled nanotweezer.

In one implementation, this disclosure provides a nanotweezer comprisinga first meta structure, a second metastructure, a microfluidic channel,a voltage sources, and a light source. The first metastructure includesa first substrate, a first electrode, a plurality of plasmonicnanostructures arranged in an array, and a trapping region laterallydisplaced from the array. The second metastructure includes a secondsubstrate and a second electrode. The microfluidic channel is positionedbetween the first metastructure and the second metastructure. Thevoltage source is configured to selectively apply an electric fieldbetween the first electrode and the second electrode. The light sourceis configured to selectively apply an excitation light to themicrofluidic channel at a first location corresponding to the array,wherein the application of the excitation light is configured to trap ananoparticle at a second location corresponding to the trapping region.

In another exemplary aspect of the present disclosure, there is provideda method of operating a nanotweezer that includes a first metastructure,a second metastructure, and a microfluidic channel positioned betweenthe first metastructure and the second metastructure. The firstmetastructure includes a first substrate, a first electrode, a pluralityof plasmonic nanostructures arranged in an array, and a trapping regionlaterally displaced from the array. The second metastructure includes asecond substrate and a second electrode. The method includes selectivelyapplying an electric field between the first electrode and the secondelectrode, selectively applying an excitation light to the microfluidicchannel at a first location corresponding to the array, and, by applyingthe electric field and the excitation light, trapping a nanoparticle ata second location corresponding to the trapping region.

In this manner, various aspects of the present disclosure provide forimprovements in at least the technical fields of quantum photonics, aswell as the related technical fields of energy production, biosensing,nano-assembly, label-free DNA sequencing, separation and analysis ofextracellular vesicles or viral particles, quantum computing, materialcharacterization, and the like.

This disclosure can be embodied in various forms, including through theuse of hardware or circuits controlled by computer-implemented methods,computer program products, computer systems and networks, userinterfaces, and application programming interfaces; as well ashardware-implemented methods, signal processing circuits, memory arrays,application specific integrated circuits, field programmable gatearrays, and the like. The foregoing summary is intended solely to give ageneral idea of various aspects of the present disclosure, and does notlimit the scope of the disclosure in any way.

Other aspects of the invention will become apparent by consideration ofthe detailed description and accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a cross-sectional view of a first example of a plasmonicnanostructure in accordance with one implementation.

FIG. 2 is a cross-sectional view of a second example of a plasmonicnanostructure in accordance with another implementation.

FIG. 3 is a cross-sectional view of a third example of a plasmonicnanostructure in accordance with yet another implementation.

FIG. 4 is an overhead plan view of an exemplary nanostructure array foruse with the nanostructures of FIGS. 1 through 3 .

FIG. 5 is an overhead plan view of another exemplary nanostructure arrayfor use with the nanostructures of FIGS. 1 through 3 .

FIG. 6 is an overhead plan view of yet another exemplary nanostructurearray for use with the nanostructures of FIGS. 1 through 3 .

FIG. 7 is a cross-sectional schematic view of a plasmonic nanostructureof FIGS. 1 through 3 demonstrating applicable forces during operation.

FIGS. 8A-8C is a plan view schematic diagraph of the particletranslation relative to a nanostructure array of FIG. 4 .

FIG. 9 is a sequence of elevation view images of an example of particlemanipulation in accordance with various aspects of the presentdisclosure;

FIG. 10A is a graph illustrating an example of trapping behavior aslongitudinal particle position relative to longitudinal velocity foreach of a plurality of AC electrical field frequencies.

FIG. 10B is a graph illustrating an example of trapping behavior as theAC electrical field frequency corresponding to lateral and longitudinalparticle positions.

FIG. 11 is a sequence of elevation view images of an example ofparticles sorting using the systems of FIGS. 1 through 6 .

DETAILED DESCRIPTION

Before any embodiments of the invention are explained in detail, it isto be understood that the invention is not limited in its application tothe details of construction and the arrangement of components set forthin the following description or illustrated in the following drawings.The invention is capable of other embodiments and of being practiced orof being carried out in various ways. Additionally, in the followingdescription, numerous details are set forth, such as circuitconfigurations, waveform timings, circuit operations, and the like, inorder to provide an understanding of one or more aspects of the presentdisclosure. It will be readily apparent to one skilled in the art thatthese specific details are merely exemplary and not intended to limitthe scope of this application.

To resolve the aforementioned issues, the present disclosure describes atype of optically controlled nanotweezers referred to herein as anopto-thermo-electrohydrodynamic tweezer (OTET). An OTET in accordancewith the present disclosure enables the trapping and dynamicmanipulation of nanometer-scaled objects at locations that are severalmicrons away from the high-intensity laser focus. At the trappinglocations, the nanoscale objects experience both negligible photothermalheating and light intensity. An OTET as described herein employs afinite array of plasmonic nanostructures illuminated with light andapplied alternating-current (AC) electric field to create aspatially-varying electrohydrodynamic potential capable of rapidlytrapping sub-10 nm biomolecules at femtomolar concentrations on-demand.In comparison to the ETP approaches described above, an OTET exploitsthe interaction between ETP flow and AC electro-osmotic (EO) flow toestablish an electrohydrodynamic potential capable of lower powertrapping at tunable trapping locations that are a sufficient distancefrom the high-intensity laser focus to prevent photo-induced damage, aswell as the sorting and/or subsequent manipulation of trapped particles.

The use of closely spaced arrays of plasmonic nanoantennas precludesachieving such on-demand fluid motion due to intrinsic thermoplasmonicconvection. However, by employing photo-induced heating of a singleplasmonic nanoantenna, on-demand fluid motion can be readily achieved,at least because intrinsic thermoplasmonic convection by a singleplasmonic nanoantenna is weak (<10 nm/s). In accordance with the presentdisclosure, micrometer-per-second nanoparticle transport velocity can beobtained by harnessing the photo-induced heating of a single plasmonicnanoantenna.

The OTET platform comprises a finite array of plasmonic nanostructuresilluminated with light and a perpendicularly-applied AC electric fieldto optically induce thermal gradients and distort the AC electric fieldlines. The coupling of the nanostructure array with light results inhighly localized and enhanced electromagnetic hotspots, which promoteslight absorption. The enhanced light absorption results in a temperaturerise and thermal gradient in the fluid. At a particular distance from anedge of the array, the forces due to the ETP flow and the forces due tothe AC electro-osmotic flow cancel one another, resulting in a stabletrapping position.

Exemplary plasmonic nanostructures are illustrated in FIGS. 1, 2, and 3and exemplary arrays are illustrated in FIGS. 4, 5, and 6 . Inparticular, FIGS. 1 through 3 each respectively illustrate partialcross-sectional views of a unit cell of the OTET. While FIGS. 1 through3 each illustrate only a single unit cell and a single nanostructure, inpractice the unit cell is repeated in a two-dimensional manner to formthe array.

In the example of FIG. 1 , an OTET 100 includes a first metastructure110 which includes a first substrate 111, a first electrode 112, and aplasmonic nanohole 113; a second metastructure 120 which includes asecond substrate 121 and a second electrode 122; a microfluidic channel130 between the first metastructure 110 and the second metastructure120; and a voltage source 140 which selectively applies an electricfield between the first electrode 112 and the second electrode 122.

The second substrate 121 and the second electrode 122 are preferablyformed of a material that is substantially transparent to light within apredetermined wavelength range. The predetermined wavelength rangeincludes a wavelength of light from a laser light source used toilluminate the OTET 100 and, in some implementations at least a portionof a wavelength of light from a white light source which may be used topermit observation and/or imaging. In some examples, the first substrate111 and the second substrate 121 are respectively formed of a glass. Insome examples, the first electrode 112 is formed of a conductivematerial capable of absorbing light at the nanohole 113, which may be ametal such as gold or may be a semiconductor material such as silicon orgeranium (including combinations and alloys). While FIG. 1 illustratesthe second substrate 121 and the second electrode 122 as separatelayers, in some examples the second substrate 121 and the secondelectrode may be integral. In some examples, the second substrate 121and/or the second electrode 122 are formed of a substantially(e.g., >90%) transparent metal, such as indium tin oxide (ITO).

In the example of FIG. 2 , an OTET 200 includes a first metastructure210 which includes a first substrate 211, a first electrode 212, and aplasmonic nanopillar 213; a second metastructure 220 which includes asecond substrate 221 and a second electrode 222; a microfluidic channel230 between the first metastructure 210 and the second metastructure220; and a voltage source 240 which selectively applies an electricfield between the first electrode 212 and the second electrode 222.

The second substrate 221 and the second electrode 222 are formed of amaterial that is substantially transparent to light within apredetermined wavelength range. The predetermined wavelength rangeincludes a wavelength of light from a laser light source used toilluminate the OTET 200 and, in some implementations at least a portionof a wavelength of light from a white light source which may be used topermit observation and/or imaging. In some examples, the first substrate211 and the second substrate 221 are respectively formed of a glass. Insome examples, the first electrode 212 and the plasmonic nanopillar 213are formed of a conductive material capable of absorbing light at thenanopillar 213, which may be a metal such as gold or may be asemiconductor material such as silicon or geranium (includingcombinations and alloys). While FIG. 2 illustrates the second substrate221 and the second electrode 222 as separate layers, in some examplesthe second substrate 221 and the second electrode may be integral. Insome examples, the second substrate 221 and/or the second electrode 222are formed of a substantially (e.g., >90%) transparent metal, such asindium tin oxide (ITO).

In the example of FIG. 3 , an OTET 300 includes a first metastructure310 which includes a first substrate 311 and a first electrode 312; asecond metastructure 320 which includes a second substrate 321 and asecond electrode 322; a microfluidic channel 330 between the firstmetastructure 310 and the second metastructure 320; and a voltage source340 which selectively applies an electric field between the firstelectrode 312 and the second electrode 322. The first electrode 312 isformed of a photoconductive material. The photoconductive material, whenilluminated at a particular portion, will generate excess carriersmaking an electrically conductive nanospot 313. The nanospots 313 may beformed in a particular pattern through the use of a spatial lightmodulator (SLM). In the presence of a lower frequency (<15 kHz or <20kHz) AC electrical field and a central heating laser beam, the nanospots313 will enable the assembly of particles at a position defined by thelight pattern and AC electrical field. The assembly can be reconfiguredby varying the shape of the light pattern array using the SLM.

The second substrate 321 and the second electrode 322 are formed of amaterial that is substantially transparent to light within apredetermined wavelength range. The predetermined wavelength rangeincludes a wavelength of light from a laser light source used toilluminate the OTET 300 and, in some implementations at least a portionof a wavelength of light from a white light source which may be used topermit observation and/or imaging. In some examples, the first substrate311 and the second substrate 321 are respectively formed of a glass.While FIG. 3 illustrates the second substrate 321 and the secondelectrode 322 as separate layers, in some examples the second substrate321 and the second electrode may be integral. In some examples, thesecond substrate 321 and/or the second electrode 322 are formed of asubstantially (e.g., >90%) transparent metal, such as indium tin oxide(ITO).

While each of FIGS. 1 through 3 illustrate an exemplary OTET of abottom-exposure configuration, in which light (excitation light and/orimaging light, for example) enters the respective microfluidic channelfrom below, the present disclosure is not so limited. For example, anOTET in accordance with the present disclosure may have a top-exposureconfiguration, in which light enters the microfluidic channel fromabove. In this configuration, the respective first metastructure shouldbe substantially (e.g., >90%) transparent to light within thepredetermined wavelength range.

In the above configurations, the nanopillar 113, the nanohole 213, andthe nanospot 313 are all examples of a plasmonic nanostructure inaccordance with the present disclosure. Preferably, a plurality ofplasmonic nanostructures are present and are disposed in an array of aparticular shape. FIGS. 4 through 6 each illustrate a plan view ofdifferent exemplary OTETs having a plurality of plasmonic nanostructuresdisposed in an array, each of which may be examples of the OTETs 100,200, and/or 300 illustrated in FIGS. 1 through 3 .

In the example of FIG. 4 , an OTET 400 includes a plurality of plasmonicnanostructures 410 disposed in a rectangular array 420. In FIG. 5 , anOTET 500 includes a plurality of plasmonic nanostructures 510 disposedin a circular array 520. In FIG. 6 , an OTET 600 includes a plurality ofplasmonic nanostructures 610 disposed in a first annular array 621 and asecond circular array 622, where the first annular array 621 and thesecond array 622 are concentric and nested. In other implementations,other array shapes may be implemented, such as elliptical, hexagonal,star-shaped, and so on. Moreover, where multiple arrays are implemented,they may be nested as illustrated in FIG. 6 , may be disposed lateral toone another, or combinations thereof.

Varying the geometry of the patterned array molds the distribution ofthe assembled objects. For example, by using the OTET 500 illustrated inFIG. 5 , the assembled objects may formed in a circular distribution ata critical distance around the circumference of the circular array 520.The trapping distance is dependent on the applied AC field frequency, aswill be described in more detail below. The assembled nanoparticles canbe patterned by applying an AC field frequency below a particularthreshold. Through the use of the above arrays, it is possible to sortnanoparticles according to their size and/or shape.

As noted above, the OTETS described herein may trap and manipulatenanoscale objects based on the interaction between AC electro-osmoticflow forces and ETP flow. FIG. 7 illustrates this principle in greaterdetail. In particular, FIG. 7 illustrates a partial cross-section of anexemplary OTET 700, which may be the same as or similar to the OTETsillustrated in FIGS. 1 through 6 and described above.

The OTET 700 includes a first metastructure 710, a second metastructure720, a microfluidic channel between the first metastructure 710 andsecond metastructure 720, and a voltage source 740 which selectivelyapplies an electric field between the first metastructure 710 and thesecond metastructure 720. The first metastructure 710 includes apatterned portion 711, which corresponds to a plurality ofnanostructures, and an edge portion 712 which does not includenanostructures. FIG. 7 also illustrates a nano-object 750 in themicrofluidic channel 730. In operation, the voltage source 740 appliesan AC electric field perpendicular to the first metastructure 710 andthe second metastructure 720, across the microfluidic channel 730. Thetopography of the patterned portion 711 results in the distortion of theapplied AC electric field to give rise to both normal and tangential ACelectrical field components. The tangential AC electrical fieldcomponent exerts Coulombic forces on the diffuse charges in theelectrical double layer induced at the interface between the first andsecond metastructures 710, 720 and the microfluidic channel 730.

This AC-field-induced motion of the diffuse charges gives rise to anelectro-osmotic motion of the fluid, and thus a force FEO on thenano-object 750 that is directed radially outward. An ETP flow is alsoinduced by the action of both the laser-induced heating of the fluidnear the patterned portion 711 and the applied AC electric field. Theresulting fluid vortex provides a force FETP directed radially inward.These two opposing microfluidic flows create a stagnation zone where thefluid velocity goes to zero, which defines a position where thenano-object 750 is trapped. As illustrated in FIG. 7 , the trappingposition is located a distance dt from the outer edge of the patternedportion 711. Because the trapping position is displaced from thelocation of the laser beam, the nano-object 750 is trapped severalmicrons away from the laser focus. While not illustrated in FIG. 7 , thenano-object 750 also experiences a force in the out-of-plane directionas a result of the interaction between the surface charge on thenano-object 750 and its image charge in the conducting plane. Thislocalizes the nano-object 750 in the out-of-plane direction.

If the laser illumination is displaced from the center of the patternedportion 711, the nano-object 750 can be translated along a path definedby the topography of the nanostructure array while still maintaining the“radial” position of the stagnation zone. This ability to structure themicrofluidic flow field using a plasmonic nanostructure array providesfor an approach to create on-demand flow fields to suppress the Brownianmotion of particles and localize a single particle near a solid surface.

FIGS. 8A through 8C illustrate this particle translation. In particular,FIGS. 8A-8C illustrate a plan view of an OTET 800, which may be the sameas or similar to the OTETs illustrated in FIGS. 1 through 7 anddescribed above. The OTET 800 includes a nanostructure array 810. InFIG. 8A, a nanoparticle 830 is initially trapped due to the presence oflaser light focused at an illumination spot 820. In FIG. 8B, theillumination spot 820 is moved in an upward direction, which results ina following motion of the nanoparticle 830 with some time lag.Afterward, in FIG. 8C, the nanoparticle 830 has been moved to a newlocation determined by the new position of the illumination spot 820.The illumination spot 820 may be moved by moving the light sourceitself, by rotating and/or translating a reflective element such as amirror, by using a plurality of reflective elements such as an SLM, andthe like.

The translation was demonstrated experimentally using an array of goldnanoholes with a diameter of 300 nm and a thickness of 120 nm on a glasssubstrate. Fabrication was performed using a template strippingapproach. Experimental demonstration of trapping was performed usingdiluted solutions of bovine serum albumin (BSA) protein with ahydrodynamic radius of 3.4 nm, as well as with 20 nm and 100 nmpolystyrene beads. The BSA protein was diluted to a concentration of 15femtomoles (fM). A linearly polarized laser beam with a wavelength of973 nm was focused to a spot size of 1.33 μm on the nanohole array usinga water immersion objective lens with a numerical aperture of 1.2.

FIG. 9 illustrates, frame-by-frame, a sequence of fast transport,trapping, and release of a single PSA protein molecule. In the firstframe, the nanohole array was illuminated with the laser light aposition indicated by the dot. Initially, no macroscopic effect wasobserved. Subsequently, an AC electric field of 83333 volts per meter(V/m) at a frequency of 10 kHz kilohertz (kHz) was applied across themicrofluidic channel, which resulted in the fast motion of the BSAprotein by the radially inward ETP flow toward the nanohole array. Notrapping occurred at this frequency. In the second and frames, the ACelectric field frequency was reduced to 3 kHz and the opposing AC EOflow caused the BSA protein molecule to be localized at a distance ofapproximately 8.6 μm from the edge of the nanohole array within 3seconds.

At this point, the trapped particle may be manipulated in one of atleast the following ways: (1) the BSA protein may be held using both thelaser and AC electric field (as in the fourth frame); (2) the BSAprotein may be released by turning off the AC electric field (as in thefifth frame) or by increasing the frequency above a threshold value,such as 10 kHz; or (3) the BSA protein may be dynamically manipulated bymoving the laser beam or translating the microscope stage as illustratedin FIGS. 8A-8C.

The trapping distance dt between the position of the trapped object andthe edge of the nanohole array can be tuned by changing the AC electricfield frequency, as illustrated in FIGS. 10A-10B. At a lower AC electricfield frequency, the radially-outward AC EO flow is increased relativeto the ETP flow, which causes the shifting of the stagnation zoneradially outward. As the frequency increases to 5 kHz, the trappingposition of the BSA protein is shifted inward to a location that iscloser to the nanostructure array.

FIG. 10A illustrates the results of a numerical simulation, and plotsthe longitudinal position (i.e., the distance from the edge of thenanostructure array) on the x-axis and the longitudinal velocity on they-axis. The stagnation zone exists at the point where the longitudinalvelocity is zero, which is shown in more detail in the inset. As can beseen from FIG. 10A, the location of the stagnation zone moves outwardwith decreasing AC electric field frequency. Thus, by tuning thefrequency, the location of the trap relative to the edge of thenanostructure array may be controlled on-demand. The particle trappingstability of the OTET may also be controlled by tuning the AC electricfield frequency, as illustrated in FIG. 10B which plots the lateralposition on the x-axis and the longitudinal position on the y-axis. Atlower frequencies, the particle surface interaction force is generallystronger, resulting in a tighter distribution of positions. This may beattributed to a phenomenon wherein, for lower frequencies, theelectrical double layer surrounding the particle has more time to besufficiently polarized by the AC electrical field.

The frequency dependence of the trapping stability may be used forsize-based sorting by an OTET, as was demonstrated experimentally usingthe same OTET as described above with regard to FIG. 9 . In particular,the OTET was used to perform the selective trapping of 20 nm polystyrenebeads from a solution containing 100 nm and 20 nm beads. FIG. 11illustrates, frame-by-frame, a sequence of size-based sorting of thebeads. In the first frame, an AC electric field with a frequency of 2.5kHz was used to trap both 20 nm beads (indicated by a box) and 100 nmbeads (indicated by a circle). When the frequency was increased to 4 kHzas shown in the third frame, the 100 nm beads were released from thetrap while the 20 nm beads remained in place. The frequency wassubsequently decreased to 3.5 kHz to ensure that the 20 nm beadsremained stably trapped.

Although the size-based sorting was demonstrating using polystyrene,this technique may be harnessed for the sorting of any desired particle,such as exosomes which range in size from 30 nm to 150 nm from apopulation of extracellular vesicles.

In demonstrating the particle trapping and manipulation behaviordescribed above, including but not limited to the images shown in FIGS.9 and 11 , a test device and system was created and utilized. Inparticular, a 5 nm thick chromium (Cr) mask was deposited on a 1.5mm×1.5 mm silicon (Si) wafer using a resistive evaporator. Subsequently,the substrate was spin-coated with 400 nm ZEP520A photoresist and bakedat 180° C. for 2 min. Electron-beam lithography (EBL) was used topattern the nanohole arrays having a radius of 150 nm and a latticeconstant of 590 nm. The array was square in shape with a dimension of 70μm. The patterned resist was developed in ZED-N50 for 2 min, rinsed withisopropyl alcohol (IPA), and blown dry in nitrogen. After 7 seconds ofdescumming, Cl2 plasma etching was applied for 75 seconds to transferthe pattern onto the Cr layer serving as the hard mask for a subsequentreactive ion etching (ME) process. RIE proceeded for 2 min to open ˜200nm deep nanoholes into the Si wafer. To ensure the whole photoresist andCr mask layers were stripped off before depositing a gold film, thepatterned silicon wafer was sonicated in acetone for 10 min, then soakedin Cr etchant for 10 min. As a result, the patterned Si wafer was formedinto a template.

Subsequently, 120 nm gold film was deposited on the template. Theresistive evaporator was again utilized to deposit the 120 nm gold filmonto the template. UV-curable epoxy was then applied onto the gold film,which was then covered with an ITO-coated glass substrate. The assemblywas then exposed under UV light at a wavelength of 324 nm for 12 min toharden the epoxy. The gold film was peeled off the Si template, afterwhich the gold film was packaged into a microfluidic channel. The usedSi template was cleaned using O2 plasma etching and gold etchant. The Sitemplate was then reused by depositing another 120 nm gold film andperforming the template stripping process again.

To package the gold nanohole array sample into a microfluidic chip, thesurface of the gold film was treated using a polymer solution for 10 minto ensure that the surface acquires a net surface charge to preventparticles from sticking to the surface. The polymer solution consists ofpoly (sodium 4-styrenesulfonate) potassium chloride (1:5) solution inwater (1:25). The sample was then flushed under deionized waterthoroughly and blown dry under N2. Finally, the gold film was sandwichedby covering it with another ITO coated glass coverslip spaced by a 120μm thick dielectric spacer to create a microfluidic channel around thepatterns.

Depending on the test, BSA or polystyrene beads were all originally of aconcentration of 1 mg/mL. BSA was diluted by 1 billion times usingdeionized water to generate a sufficiently-sparse solution suitable forsingle molecule manipulation. The final concentration of the BSAmolecule was 15 fM. The 20 nm polystyrene solution was diluted by 10million times, whereas the 100 nm polystyrene solution was diluted by 1million times.

Trapping and imaging was performed using a custom fluorescent imagingand optical trapping microscope based on a Nikon Ti2-E™ invertedmicroscope. A high quantum-efficiency sCMOS camera, a Photometrics PRIME95B™, was used to acquire images at a frame rate of 2.5 frames persecond (fps). The trapped fluorescent polystyrene beads were excitedunder green light from a filtered broadband fluorescent illuminationlamp, Nikon INTENSILIGHT C-HGFI™. The emitted red light was collectedthrough the same objective lens and imaged on the camera. The nanoholearray was excited by a 973 nm semiconductor diode laser, ThorlabsCLD1015™. The laser beam was focused with a Nikon™ 60× water-immersionobjective lens having a numerical aperture of 1.2. The AC electric fieldwas supplied by a dual-channel function generator, BK Precision 4047B™.Electrical conductivity and electrophoretic mobility were measured usingAnton Paar Litesizer 500™. The electrical conductivity of the BSAprotein sample was 3.3 mS/m, while its electrophoretic mobility was −3(μm·cm)/(V·s).

The electromagnetic simulation (see, e.g., FIGS. 10A-10B) was performedusing a full-wave simulation formalism in Lumerical (TD) finitedifference time domain (FDTD) software. Periodic boundary conditionswith a 590 nm lattice constant was applied to mimic an infinite array ofnanoholes. Perfectly matched layers were placed at the top and bottom ofthe domain to prevent backscatter from boundaries. A linearly-polarizedplane wave served as the light source. Absorption was calculated as(1−R−T), where R refers to the reflectance and T refers to thetransmittance. A 3D COMSOL model was established to solve the heattransfer and fluid dynamics problem. A prescribed temperature of 293.15K was set at the boundaries for solving heat transfer. The ACelectro-osmotic flow was modeled using a slip boundary condition on thesurface of the nanohole array. The slip velocity was the electro-osmoticslip velocity vector u, given by the expression u=μ_(eo)E_(t), whereμ_(eo)=−(∈_(r)∈₀. ζ)(μ) is the electro-osmotic mobility, ∈_(r) is therelative permittivity, ∈₀ is the permittivity of free space, ζ is thezeta potential, and μ is the dynamic viscosity of the liquid.E_(t)=E−(E·n)n and E is calculated by solving the Poisson equation. Thezeta potential used was calculated from the measured values. The no-slipboundary condition u=0 was set on all other boundaries. The thermalproperties of glass, gold, and water were adapted from the COMSOLmaterial library. The measured electrical conductivity of liquid wasused. The relative permittivity of water was set as 78.

The above-described techniques provide a method to trap and dynamicallymanipulate nanoscale (e.g., sub-10 nm) particles and biomolecules atfemtomolar concentrations within a few seconds at a trapping positionseveral microns away from the high-intensity laser focus by using aplasmonic nanostructure array. The above-described techniques may alsoachieve size-based sorting of sub-100 nm objects. Thus, an OTET inaccordance with the present disclosure may be used as a tool for thebiological sensing of analytes at low levels.

Various aspects of the present disclosure may be practically implementedin several fields. For example, the present disclosure may be appliedfor ultra-low detection limit biological sensing, single moleculeanalysis to determine the diffusion coefficient and electrokineticmobility of proteins in solution, size-based sorting of nanoscaleobjects such as exosomes, and so on.

With regard to the processes, systems, methods, heuristics, etc.described herein, it should be understood that, although the steps ofsuch processes, etc. have been described as occurring according to acertain ordered sequence, such processes could be practiced with thedescribed steps performed in an order other than the order describedherein. It further should be understood that certain steps could beperformed simultaneously, that other steps could be added, or thatcertain steps described herein could be omitted. In other words, thedescriptions of processes herein are provided for the purpose ofillustrating certain embodiments, and should in no way be construed soas to limit the claims.

Accordingly, it is to be understood that the above description isintended to be illustrative and not restrictive. Many embodiments andapplications other than the examples provided would be apparent uponreading the above description. The scope should be determined, not withreference to the above description, but should instead be determinedwith reference to the appended claims, along with the full scope ofequivalents to which such claims are entitled. It is anticipated andintended that future developments will occur in the technologiesdiscussed herein, and that the disclosed systems and methods will beincorporated into such future embodiments. In sum, it should beunderstood that the application is capable of modification andvariation.

All terms used in the claims are intended to be given their broadestreasonable constructions and their ordinary meanings as understood bythose knowledgeable in the technologies described herein unless anexplicit indication to the contrary in made herein. In particular, useof the singular articles such as “a,” “the,” “said,” etc. should be readto recite one or more of the indicated elements unless a claim recitesan explicit limitation to the contrary.

The Abstract of the Disclosure is provided to allow the reader toquickly ascertain the nature of the technical disclosure. It issubmitted with the understanding that it will not be used to interpretor limit the scope or meaning of the claims. In addition, in theforegoing Detailed Description, it can be seen that various features aregrouped together in various embodiments for the purpose of streamliningthe disclosure. This method of disclosure is not to be interpreted asreflecting an intention that the claimed embodiments require morefeatures than are expressly recited in each claim. Rather, as thefollowing claims reflect, inventive subject matter lies in less than allfeatures of a single disclosed embodiment. Thus the following claims arehereby incorporated into the Detailed Description, with each claimstanding on its own as a separately claimed subject matter.

What is claimed is:
 1. A nanotweezer, comprising: a first metastructureincluding a first substrate, a first electrode, a plurality of plasmonicnanostructures arranged in an array, and a trapping region laterallydisplaced from the array; a second metastructure including a secondsubstrate and a second electrode; a microfluidic channel between thefirst metastructure and the second metastructure; a voltage sourceconfigured to selectively apply an electric field between the firstelectrode and the second electrode; and a light source configured toselectively apply an excitation light to the microfluidic channel at afirst location corresponding to the array, thereby to trap ananoparticle at a second location corresponding to the trapping region,wherein the plurality of plasmonic nanostructures are arranged in aplurality of rows and a plurality of columns within the array, whereineach of the rows within the array are substantially orthogonal to eachof the columns within the array, and wherein a first pitch between eachplasmonic nanostructure and an adjacent plasmonic nanostructure withineach row of the plurality of rows is substantially the same.
 2. Thenanotweezer according to claim 1, wherein a frequency of the electricfield is less than 10 kHz.
 3. The nanotweezer according to claim 1,wherein the first electrode includes gold, and respective ones of theplurality of plasmonic nanostructure are nanoholes disposed in the firstelectrode.
 4. The nanotweezer according to claim 1, wherein the secondelectrode is formed of ITO.
 5. The nanotweezer according to claim 1,wherein the light source is a laser light source.
 6. The nanotweezeraccording to claim 1, wherein the nanoparticle is a biomolecule.
 7. Thenanotweezer according to claim 6, wherein the biomolecule has a size ofless than or equal to 10 nm.
 8. The nanotweezer according to claim 1,wherein a second pitch between each plasmonic nanostructure and anadjacent plasmonic nanostructure within each column of the plurality ofcolumns is substantially the same.
 9. The nanotweezer according to claim8, wherein the first pitch is substantially equal to the second pitch.10. The nanotweezer according to claim 9, wherein the plurality ofplasmonic nanostructures includes a plurality of nanoholes formed in thefirst electrode.
 11. The nanotweezer according to claim 9, wherein theplurality of plasmonic nanostructures includes a plurality of plasmonicnanopillars protruding from a surface of the first electrode, whereinthe surface faces the microfluidic channel.
 12. The nanotweezeraccording to claim 1, wherein the array is a uniform planar array. 13.The nanotweezer according to claim 12, wherein the uniform planar arrayincludes a rectangular array.
 14. The nanotweezer according to claim 12,wherein the uniform planar array includes a circular array.
 15. Thenanotweezer according to claim 12, wherein the uniform planar arrayincludes a first array nestled within a second array.
 16. Thenanotweezer according to claim 15, wherein: the first array is a firstcircular array, the second array is a second circular array, and adiameter of the first array is less than a diameter of the second array.